Abstract Summary Evidence suggests the auditory brain--the tracts and nuclei throughout the brain involved with processing and interpreting sound--is affected in Alzheimer?s disease and related dementias (ADRD). Additionally, some studies suggest tests of the auditory brain (i.e. central auditory processing tests) may provide an early maker of cognitive impairment. The key new concept presented here is using the auditory network to assess the CNS in ADRD. Turning the flow of auditory information from a stream of nerve signals into interpretable speech is a demanding neurological task. Speech perception, particularly interpreting speech-in-noise (i.e. the ?cocktail party problem?), involves several cortical and subcortical centers. Tests that assess that ability to process speech and timing information (speech-in-noise, digits-in- noise, or gap detection testing) or that assess the overall neurophysiological signals resulting from this process (frequency following response (FFR)), are evaluating CNS function. These tests may be useful in ADRD because the ability to detect ADRD early, and to measure progress, are important for studying, tracking, and treating these disabling conditions. In our current NIH-funded research in both Tanzania and Shanghai, China we have shown that HIV+ individuals have signs of a central auditory processing deficit and show a strong negative relationship between cognitive performance and the ability to understand speech in background noise (despite normal peripheral hearing determined by audiometric thresholds). They also have higher gap detection in noise thresholds (another sign of a central auditory deficit), and changes on neuro-electrophysiological tests (frequency-following response). This supplement will take our approach to assessing neurocognitive function through the central auditory system in HIV+ patients and apply it to individuals with mild cognitive impairment (MCI). Central auditory tests can offer reliable, quantitative, time efficient, and repeatable ways to assess central nervous system function. These tests could be potentially be used to detect and track central nervous system dysfunction in patients with MCI who may be on the pathway to Alzheimer?s. In some settings these tests may offer advantages over neuropsychological testing which can be time-consuming, labor-intensive, and sometimes stressful for the patient. Central auditory changes might appear earlier than, or independently from, other neurological or neuropsychological test findings, so detecting these changes could complement or enhance current testing methods. The extension of central auditory testing into assessing neurological effects of AD is novel. Some of the tests, such as the frequency following response require no input on the part of the patient (it measures the electrophysiological responses to complex sounds (syllables) presented to the ear). Use of this technology would be particularly innovative, since it may circumvent problems with learning or understanding behavioral central auditory tests. If successful, the use of these tests has the potential to offer new ways to track and assess ADRD and show whether central auditory tests could serve as a ?window? into the CNS in ADRD.